Biomedical subjects

D K Kim

Publications and source records attributed to D K Kim.

At least 253 records · Page 14Linked to original sources

PubMed1994

Annexin-I inhibits phospholipase A2 by specific interaction, not by substrate depletion.

Annexin-I is a calcium dependent phospholipid binding and phospholipase A2 (PLA2) inhibitory protein. A 'substrate depletion' model has been proposed for the mechanism of PLA2 inhibition by annexin-I in studies with 14 to 18 kDa PLA2s. Herein, we have studied the inhibition mechanism using 100 kDa cytosolic PLA2 from porcine spleen. The inhibition has been measured at various substrate and calcium ion concentrations. The pattern of PLA2 inhibition by annexin-I was consistent with a 'specific interaction' mechanism rather than the 'substrate depletion' model. Apparent contraction with previous studies can be explained by the calcium-dependent binding of annexin-I to the substrate.

Animals↗

PubMed1994

Unilateral vestibular schwannoma in a child with prior orbital rhabdomyosarcoma.

In the absence of neurofibromatosis, vestibular schwannomas (acoustic neuromas) are rarely found in children. We report a case of a 13-year-old boy who presented with unilateral vestibular schwannoma 11 years after resection of an orbital rhabdomyosarcoma. The coincidence of these tumors has not been previously reported.

Adolescent↗

PubMed1994

Characteristic morphologic abnormality of harlequin ichthyosis detected in amniotic fluid cells.

We have examined cells from amniotic fluid obtained at 17 and 21 weeks' gestation and fetal skin biopsy samples from a fetus at risk of harlequin ichthyosis by light and electron microscopy. Clumps of abnormally keratinized cells that had a large number of lipid droplets in the cytoplasm were seen within both the 17- and 21-week amniotic fluid cell pellets. The cells in these clumps were similar to the thick layers of keratinized cells observed in the skin biopsy and autopsy samples. Morphologic examination of the fetal skin biopsy samples obtained at 21 weeks gestation revealed the characteristic changes of harlequin ichthyosis. The intraepidermal portions of hair canals had an excessive number of layers of keratinized cells. Normal lamellar granules were absent but abundant membrane-bound vesicles of a similar size and a number of dense bodies were observed in the cells of the upper intermediate layers of the epidermis. Autopsy skin samples of the terminated fetus at the twenty-third week of gestation showed structural changes that corresponded to those of the amniotic fluid cells and the fetal skin biopsy samples, although the periderm was gone in all the regions. Our findings of amniotic fluid indicate that the characteristic epidermal abnormality of harlequin ichthyosis has been expressed at 17 weeks gestation in some parts of the body or structures of fetal skin (e.g., hair canals) that keratinize before interfollicular epidermis. Moreover, the results suggest that harlequin ichthyosis can be detected in utero by morphologic analysis of amniotic fluid cells obtained by amniocentesis.

Adult↗

PubMed1994

Clinical analysis of 40 cases of childhood-onset Behçet's disease.

Behçet's disease is a chronic, relapsing, idiopathic, multi-system condition characterized by mucocutaneous, ocular, gastrointestinal, articular, vascular, urogenital, and neurologic involvement. Usually the onset occurs between 20 and 30 years of age; it is very uncommon in children. We analyzed 40 cases of childhood-onset Behçet's disease. The male:female ratio was 0.67. The most frequent major sign was oral ulceration, appearing in all patients. Other major signs were genital ulcers (33 patients), skin lesions (29), and ocular lesions (11). The average time interval between the initial oral ulceration and the second major manifestation was 8.8 years. After the second major manifestation, the third and fourth features rapidly developed within one to two years. The most frequent minor sign was arthritis, occurring in 11 of 40 patients. Intestinal, neurologic, and renal involvement was also present. From our results, we concluded that oral ulceration, which is the most common initial manifestation, should not be neglected in children, since it may signal Behçet's disease.

Age of Onset↗

PubMed1994

Role of 100-kDa cytosolic PLA2 in ACh-induced contraction of cat esophageal circular muscle.

We have shown that acetylcholine (ACh)-induced contraction of esophageal circular muscle cells is mediated by activation of protein kinase C (PKC). We now examine the role of phospholipase A2 (PLA2). ACh increases [3H]arachidonic acid release in esophageal but not in lower esophageal sphincter (LES) muscle. In addition, ACh-induced contraction of esophageal but not of LES cells was reduced by the PLA2 antagonist dimethyleicosadienoic acid and by antiserum to a 100-kDa cytosolic PLA2 (cPLA2). These data suggest that the 100-kDa cPLA2 plays a role in ACh-induced contraction of esophageal but not of LES muscle. In esophageal cells, arachidonic acid produced by PLA2 caused little contraction by itself but potentiated contraction induced by the PKC agonist diacylglycerol (DAG). The free fatty acids linoleic acid and linolenic acid also potentiated DAG-induced contraction. Indomethacin and nordihydroguaiaretic acid had no effect on arachidonic acid-induced potentiation of DAG. The potentiation of DAG-induced contraction by arachidonic acid was inhibited by the PKC inhibitor H-7, but it was not affected by the calmodulin inhibitor CGS-9343B. We conclude that a 100-kDa cPLA2 participates in ACh-induced esophageal contraction by producing arachidonic acid and potentiating DAG-induced activation of a PKC-dependent pathway.

Acetylcholine↗

PubMed1994

Myocardial energy metabolism and morphology in a canine model of sepsis.

The mechanism responsible for sepsis-induced myocardial depression is not known. To determine if sepsis-induced myocardial depression is caused by inadequate free energy available for work, we studied myocardial energy metabolism in a canine model of sepsis. Escherichia coli-infected (n = 18) or sterile (n = 16) fibrin clots were implanted intraperitoneally into beagles. Myocardial function and structure was assessed using radionuclide ventriculograms, echocardiograms, and light and electron microscopy. The adequacy of energy metabolism was evaluated by comparing catecholamine-induced work increases [myocardial O2 consumption (MVO2) and rate pressure product (RPP)] with a simultaneously obtained estimate of intracellular free energy [phosphocreatine-to-adenosine triphosphate ratio (PCr:ATP)] determined by 31P-magnetic resonance spectroscopy. When compared with control animals, septic animals had a decrease in left ventricular ejection fraction (EF, P < 0.0001) on day 1 and fractional shortening (FS, P < 0.0003) on day 2 after clot implantation. On day 2, neither septic nor control animals had statistically significant decreases in PCr:ATP, despite catecholamine-induced increases in MVO2 and RPP (mean maximal increases in septic animals 135 +/- 31 and 51 +/- 10%, respectively). Light and electron microscopic findings showed that hearts of septic animals, compared with control animals, had a greater degree of morphological abnormalities. Thus, in a canine model of sepsis with alterations in myocyte ultrastructure and documented myocardial depression (decreased EF and FS), intracellular free energy levels (PCr:ATP) were maintained despite catecholamine-induced increases in myocardial work (increased MVO2 and RPP), suggesting high-energy synthetic capabilities are not limiting cardiac function.

Adenosine Triphosphate↗

PubMed1994

Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis.

Angiotensin II (Ang II) promotes growth of vascular smooth muscle cells in vitro. Consistent with this, Ang II enhances neointimal proliferation in vivo after vascular injury, while angiotensin converting enzyme (ACE) inhibitors attenuate this process. Since tissue ACE plays a key role in the control of local Ang II production, we examined whether vascular injury resulted in an increase in vascular ACE expression that may result in increased Ang II production. Abdominal aorta of Sprague-Dawley rats were injured with a 2 French balloon catheter. Morphometrical changes, ACE enzymatic activity, and localization of ACE by immunohistochemistry in injured and uninjured aorta were analyzed. Vascular ACE activity in the injured aorta was significantly higher than in the uninjured aorta, while serum and lung ACE levels were not different between the two groups. The cellular distribution of the ACE protein in the neointima was similar to that of alpha smooth muscle actin but differed from those of endothelial (von Willebrand factor) or monocytes/macrophages (ED-1) markers, demonstrating that ACE was expressed in neointimal smooth muscle cells. These data demonstrate that vascular injury results in the induction of vascular ACE and suggest that the inhibition of vascular ACE may be important in the prevention of restenosis after balloon injury.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

H19, a developmentally regulated gene, is reexpressed in rat vascular smooth muscle cells after injury.

Vascular smooth muscle cell migration, proliferation, and differentiation are central to blood vessel development. Since neointimal formation after vascular injury may require the reexpression of a smooth muscle developmental sequence, we examined the expression of H19, a developmentally regulated gene, in rat blood vessels. Expression of the H19 gene is associated with the differentiation process that takes place during development of many tissues. Consistent with this, H19 was highly expressed in the 1-d-old rat aorta but was undetectable in the adult. H19 transcripts were only minimally detected in uninjured carotid artery but were abundant at 7 and 14 d after injury and were localized by in situ hybridization, primarily to the neointima. H19 transcript were undetectable in proliferating neointimal cells in culture but became highly abundant in postconfluent, differentiated neointimal cells. H19 transcripts were only minimally expressed in adult medial smooth muscle cells grown under the identical conditions. Thus, H19 may play an important role in the normal development and differentiation of the blood vessel and in the phenotypic changes of the smooth muscle cells, which are associated with neointimal lesion formation. The vascular injury model may be a useful system to use in examining the function of H19.

Aging↗

PubMed1994

The utilization of Doppler ultrasonography with color flow mapping in the diagnosis and evaluation of malignant trophoblastic tumors.

The Doppler ultrasound with color flow mapping image has been recently applied for the evaluation of gynecologic diseases, in particular, malignant trophoblastic tumors with the characteristic abundant blood flow. Doppler color flow mapping of uterine artery and intratumoral blood vessels was performed at a regular interval in all 26 patients including 3 cases of lost for follow up. Systolic/diastolic (S/D) ratio representing blood flow was measured in 19 cases of malignant trophoblastic tumors and 7 cases of hydatidiform mole diagnosed at the department of Obstetrics and Gynecology, Yonsei University, College of Medicine. The initial mean S/D ratio and standard deviation(SD) of uterine artery in 11 remitted and 5 non-remitted patients were 2.72 +/- 1.31 and 2.69 +/- 1.80, respectively. No significant difference was noted between two groups. However, the final S/D ratio of uterine artery in remitted group showed significantly higher values than non-remitted group, of which values were 6.23 +/- 2.38 and 3.08 +/- 1.54, respectively (P < 0.05). In aspect of blood flow changes in malignant trophoblastic tumors after chemotherapy, remitted group showed entirely disappeared blood flow, while non-remitted group had persistent blood flow. The mean S/D ratio and SD measured in hydatidiform mole patients were 5.43 +/- 1.65, of which value reflects higher resistance than malignant trophoblastic tumors. Also blood flow was not detected in all cases. This study suggests that color flow mapping Doppler ultrasound can be a useful method in diagnosing and monitoring the treatment in malignant trophoblastic tumors along with the conventional serum beta-hCG titration.

Adult↗

PubMed1994

General pharmacology of cis-malonato[4R,5R)-4,5-bis-(aminomethyl)-2-isopropyl-1,3- dioxolane]platinum(II).

The general pharmacological properties of cis-malonato-[(4R,5R)-4,5- bis(aminomethyl)-2-isopropyl-1.3-dioxolane]platinum(II) (SKI 2053R, CAS 146665-77-2), a new potential anticancer agent, were investigated in mice, rats, guinea pigs, rabbits, cats and dogs. Intravenous administration of SKI 2053R had no effect on the central nervous system. SKI 2053R had no effect on the autonomic nervous system and smooth muscles except that it slightly inhibited the spontaneous motility of isolated rabbit ileum at a concentration of 5 x 10(-5) g/ml. SKI 2053R did not adversely affect the respiratory-cardiovascular system, gastrointestinal system, neuromuscular junction, or renal function. SKI 2053R did not significantly alter the levels of serum glucose, serum free fatty acid and plasma lactate, and did not induce hemolysis. SKI 2053R did not affect blood coagulation mechanism and liver function. SKI 2053R did not exhibit anti-inflammatory activity. It was observed that SKI 2053R increased the formation of hemolytic plaque by spleen cells of sensitized mice at high doses (10 mg/kg and 35 mg/kg). Therefore, it is concluded from these general pharmacological studies that SKI 2053R at the doses showing antitumor activity does not induce severe adverse effects on the central nervous, autonomic nervous, respiratory-cardiovascular, gastrointestinal, peripheral nervous, and other systems in experimental animals.

Animals↗

PubMed1993

Purification of a 100 kDa phospholipase A2 from spleen, lung and kidney: antiserum raised to pig spleen phospholipase A2 recognizes a similar form in bovine lung, kidney and platelets, and immunoprecipitates phospholipase A2 activity.

Phospholipase A2 (PLA2) plays a key role in the production of intracellular and extracellular chemical mediators such as arachidonic acid, eicosanoids and platelet-activating factor, which modulate membrane channel activity, signal transduction, are vasoactive and chemotactic, and are implicated in many pathophysiological mechanisms of inflammation and tissue injury. We previously identified, purified and characterized an arachidonic acid-selective cytosolic 100-110 kDa PLA2 from bovine platelets and rat kidney that is activated during cell stimulation. The purification schemes previously published resulted in low yields of enzyme, insufficient for extensive biochemical characterization. We report the purification of a large-molecular-mass (100 kDa) PLA2 from pig spleen, bovine kidney and bovine lung, using a novel large-scale purification scheme. The enzyme was purified to near homogeneity from an acidified extract obtained from 4.8 kg of pig spleen by sequential use of DEAE-cellulose anionic exchange, Butyl-Toyopearl hydrophobic chromatography and DEAE-5PW h.p.l.c., and further purified by non-denaturing PAGE. This purification scheme will permit the preparation of quantities of purified native enzyme sufficient to study its properties and regulation. To generate antiserum against the PLA2 enzyme, the 100 kDa protein was excised and electroeluted from SDS/PAGE gels of the active fractions after DEAE-5PW h.p.l.c., and this was used as antigen. This polyclonal antibody against pig spleen 100 kDa PLA2 protein reacted with 100 kDa bands in preparations partially purified from bovine platelets, kidney and lung as well as pig spleen, and immunoprecipitated PLA2 activity from these sources. The antibody also immunoprecipitated a 100 kDa protein from cytosolic fractions of cultured renal mesangial cells, human erythroleukaemia cells and human monocytic U937 cells. Considerable PLA2 activity was present in the immunoprecipitates. To our knowledge this antibody is unique in its ability to permit measurement of PLA2 activity in the immunoprecipitate itself, and will be a useful tool for the study of the regulation and the activation mechanisms of the native PLA2 enzyme.

Animals↗

PubMed1993

Analysis of water-macromolecule proton magnetization transfer in articular cartilage.

These studies were designed to establish which structural elements of cartilage are responsible for proton magnetization transfer between water (Hf) and macromolecules (Hr) observed in MRI studies on articular cartilage. Saturation transfer techniques were used to monitor magnetization transfer in vitro on samples of the two major constituents of cartilage: collagen and proteoglycan. Articular cartilage samples were also evaluated in vitro before and after the removal of the proteoglycan fraction. Isolated hydrated collagen exhibited a significant proton magnetization transfer rate with water. In contrast, proteoglycans exhibited no proton magnetization transfer. Articular cartilage, in vitro, exhibited a high degree of magnetization transfer with water protons consistent with previous MRI studies in vivo. Enzymatic removal of proteoglycan from the cartilage did not alter the magnetization transfer rate between Hr and Hf. These data demonstrate that the structure and concentration of the collagen matrix are the predominant determinants of the magnetization transfer process in articular cartilage with little or no contribution from proteoglycans. This specificity of the magnetization transfer effect may prove useful in the noninvasive evaluation of cartilage composition and structure in vivo.

Animals↗

PubMed1993

Mechanical properties of a Ti-6A1-4V dental implant produced by electro-discharge compaction.

Cylindrical, porous-surfaced implants were fabricated from Ti-6A1-4V atomized powders by an electro-discharge compaction technique (EDC). Input energy (1-2.5 kJ/g powder) was used to produce implant compacts having a solid core surrounded by a porous layer. The solid core size, neck size between core and particle, neck size between particles, and pore size in the porous layer varied as input energy was changed. Compression tests were carried out to evaluate the mechanical properties of the EDC compacts. The yield strength ranged from 270 to 530 MPa and the ultimate compressive strengths ranged from 390 to 600 MPa. The yield strengths for solid core, core-particle and particle-particle interfaces remained constant at 755 MPa regardless of input energy. The endurance limits estimated from these results were 190-310 MPa, which were higher than the reported values for sintered titanium implants. Microhardness testing revealed that hardness was independent of input energy and the position where the testing indentation was applied. The average hardness of the compacts was 3430 MPa.

Aluminum↗

PubMed1993

Statistical models for analysing time-to-occurrence data in radiobiology and radiation oncology.

Two different methods for analysing late complications data are contrasted and compared. The two methods are the Cox Proportional Hazards model and the Mixture model. The potential limitations of both methods are described together with the circumstances in which one or the other of the methods is preferable. The results from the two methods of analysis will usually be qualitatively similar and frequently quantitatively similar. For estimating the ratio of parameters, such as the alpha/beta ratio if the linear-quadratic model holds, the Cox model is the preferred method. For estimating the proportion with complications by a given follow-up time, the Mixture model is the preferred method. For data, such as from experimental animals, in which there is little censoring during the time period of interest, the Mixture model will usually be the better analysis. In contrast, for data, such as clinical data, in which there is a lot of censoring throughout the time period in which complications occur, the Cox model will usually give a more reliable analysis especially in situations where there are a small number of complications. Both methods are applied to a mouse spinal cord data set and to a clinical head and neck data set. The bias, efficiency, and coverage rate of confidence intervals and robustness of the two methods are compared in a Monte Carlo simulation.

Humans↗

PubMed1993

Hypertrichosis universalis congenita: a separate entity, or the same disease as gingival fibromatosis?

Hypertrichosis universalis congenita is an extremely rare disorder characterized by generalized hypertrichosis. It is generally accepted as being inherited as an autosomal dominant trait with varying expression. Many aspects of this disease are still unknown. Several reports associating hypertrichosis and gingival fibromatosis raise the question of whether they are separate entities or the same disease with different expressions of the underlying process. Hypertrichosis universalis congenita occurred in a 6-year-old girl without known family history. Her facial features were simian-like and her gingiva was moderately hyperplastic. We pose the question of whether or not these phenomena are related.

Child↗

PubMed1993

Detection of proliferating cell nuclear antigen in gliomas and adjacent resection margins.

We describe a technique for estimating the number of proliferating cells in gliomas and adjacent resection cavities after tumor removal. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Anti-PCNA antibody staining provides a semiquantitative estimate of the number of proliferating cells found in fixed tissue embedded in paraffin. The extent of the staining of tumor cells of glioblastoma multiforme, anaplastic astrocytomas, low-grade gliomas, and other lesions of the brain with anti-PCNA antibody is correlated with the histological diagnosis. In addition, the labeling of the margins after resection of gliomas and other lesions with anti-PCNA antibody is also associated with the histological diagnosis of the lesion. This technique may be useful in estimating the "biological" extent of resection and in predicting the recurrence patterns of gliomas.

Adolescent↗

PubMed1993

Dose-survival curves, alpha/beta ratios, RBE values, and equal effect per fraction for neutron irradiation of jejunal crypt cells.

Jejunal crypt cell survival after regimens of one, two, three and five fractions was used to reconstruct composite single-dose survival curves for neutrons of five different energies. There is no obvious shoulder, but there is a gradual divergence from linearity that is most evident at low levels of cell survival (high doses). The effect of dose fractionation is relatively small, especially at the low doses characteristic of each treatment session in neutron radiotherapy. The alpha/beta values for the linear-quadratic survival curves range from 27 to 40 Gy. The curves for neutrons are different from the curves for gamma rays mainly in their alpha coefficients, as predicted by Kellerer and Rossi's theory of dual radiation action, but both alpha and beta values are higher the lower the mean neutron energy, which is not consistent with the theory. The ratio of alpha coefficients reported here for various neutron beams to those for gamma rays reported elsewhere ranges between 3.2 and 4.6. This range of values represents the maximum limits for RBEn/gamma values (at very low doses), and is sometimes referred to as RBEm. These values increase with decreasing neutron energy. The ratios of beta coefficients for neutron and gamma-ray survival curves were lower than the alpha ratios, ranging between 0.9 and 1.9, although not reliably distinguished from 1.0. Each of a series of equal dose fractions given at 3-h intervals produced a constant (logarithmic) decrease in cell survival as evidenced by the consistency of the estimate of cell survival from a certain single dose fraction, regardless of the level of cell survival (number of dose fractions) from which the estimate was made. Even more significant than the overlap of individual data points is the excellent fit of all the data to survival curves reconstructed on the assumption of an equal effect per fraction. An implication of these results is that, with neutrons, too little unrepaired injury persists at 3 h to influence the response to a subsequent exposure measurably.

Animals↗

PubMed1992

Estrogen and progesterone receptor assay in carcinoma of the cervix with monoclonal antibodies.

The normal cervix has been shown to contain estrogen and progesterone receptors (ER and PR), but there have been controversial reports on the presence of these receptors in cervical carcinoma. Thus to explore the relationships between the steroid receptor status and cervical carcinoma, tissues of 34 patients with invasive cervical carcinoma prior to treatment and 30 cases of control who underwent hysterectomy due to benign gynecologic diseases at Yonsei Medical Center were analyzed for ER and PR using immunocytochemical assay with monoclonal antibodies and the results were compared with those of conventional steroid binding assay. ER and PR were positive in 65 and 71% of all tumors, respectively, and 59% of the cases were positive for both receptors simultaneously. No significant difference in receptor levels was noted when stratified according to menopausal status or clinical stage. With regard to tumor size, lesions greater than 3 cm had significantly lower receptor positivity when compared with the control. For the histological cell types, a statistically significant higher mean ER level was noted in adenocarcinoma compared to squamous cells. Even though the potential therapeutic significance of these findings is not yet known, they are consistent with the concept that steroid receptors can be used as a guide to endocrine therapy with respect to other prognostic parameters. However, the small number of advanced-stage carcinomas and the absence of data regarding survival rate in this study preclude any definite conclusions.

Adult↗